All About Wild-Type ATTR Amyloidosis and Why It Causes Heart Problems

Wild-type ATTR amyloidosis mostly occurs in males and often targets the heart and nerves.

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All forms of amyloidosis are caused by the abnormal folding of cellular proteins. In the case of wild-type ATTR amyloidosis, this abnormal folding happens to the same protein molecules that are affected by some heredity forms of amyloidosis. But unlike those hereditary forms of amyloidosis, wild-type ATTR is not caused by a genetic mutation. (1)

Unfortunately, there’s no way to explain what causes wild type ATTR amyloidosis without diving into some tricky organic chemistry.

Wild-Type ATTR Amyloidosis Is Linked to Aging and Heart Problems

The “TTR” in wild-type ATTR stands for transthyretin, which is a type of blood protein made by the liver that helps transport some hormones and vitamins to the parts of the body that need them, says Raymond Comenzo, MD, a professor at the Tufts University School of Medicine and the director of the school’s John C. Davis Myeloma and Amyloid Program. For example, transthyretin helps move both thyroid hormone and vitamin A through the bloodstream. (2)

In people with hereditary forms of ATTR amyloidosis, the disease stems from a mutation in the genes that alters the function of transthyretin. But in wild-type ATTR, it’s not a mutation in the gene that causes this error. Instead, a normal form of transthyretin (known as “wild type”) becomes prone to misfolding as a person ages, according to research published in 2017 in the European Heart Journal. (3)

Wild-type ATTR amyloidosis is much more common in males than females, with more than 90 percent of cases occurring in men, according to research published in 2016 in the Journal of the American College of Cardiology. (4) Experts don’t know why the disease’s prevalence is so lopsided.

There’s also some evidence that wild-type ATTR amyloidosis is a common driver of heart trouble, and Comenzo says it’s likely that wild-type ATTR is not as rare as other types of the disease — though it’s still rarely diagnosed.

While heart disease is one of the most widespread conditions among seniors, its cause is often never known. It’s possible that amyloidosis — including wild-type ATTR — is causing or contributing to heart problems in a significant number of cases. (5) But it’s important to note that the prognosis for most people with wild-type ATTR is positive. This type of amyloidosis progresses slowly, and many individuals will never experience symptoms. (6)

In men, it’s estimated that up to 1 percent of those over age 80 have misfolded amyloid proteins as a result of wild-type ATTR. But of this 1 percent, only about one in four will experience symptoms. Experts know all this thanks to autopsy reports that have turned up wild-type amyloid deposits in the hearts and tissues of deceased men — many of whom never had any symptoms. (3)

What Are the Symptoms of Wild-Type ATTR Amyloidosis?

The heart and nerves are the most common targets of harmful protein buildup in patients with wild-type ATTR amyloidosis. This buildup can cause a variety of symptoms, though some are much more common than others. (1)

In 50 percent of people with the condition, these amyloid proteins accumulate in the tissues of the heart. (2) This can lead to problems with the way the heart muscle functions, and can cause symptoms including: (1)

If the protein buildup happens in the nerves, this can lead to a loss of feeling, pain, or tingling in a person’s arms or legs. In particular, carpal tunnel syndrome — a numbness or tingling in the hand and arm — may show up among people with wild-type ATTR amyloidosis. In fact, carpal tunnel syndrome is often the earliest symptom of the disease. (1)

In a small fraction of individuals, wild-type ATTR can cause protein accumulation in a person’s bladder, lungs, or bowels. But these patients typically don’t have any symptoms as a result of this buildup. (1)

Wild-Type ATTR Amyloidosis Was Previously Known as Senile Systemic Amyloidosis

In the past, wild-type ATTR amyloidosis has been called by a few names that are no longer used. One of them is “senile systemic amyloidosis,” and another is “senile cardiac amyloidosis.” Both got their names because the type of amyloid buildup was thought to be a product of old age. (3)

In general, the terms “senility” and “senile” are no longer used because doctors now understand that heart disease, dementia, and other conditions that tend to strike seniors are caused by underlying problems, and are not considered a normal process of aging.

How Is Wild-Type ATTR Amyloidosis Diagnosed and Treated?

If a patient is showing symptoms of amyloidosis, blood tests coupled with either bone or organ scans can in some cases allow doctors to make a definitive diagnosis. In other cases, a doctor may need to biopsy a patient’s tissues to determine whether amyloidosis is to blame, and if so, what type of the disease is present. (1)

Additionally, genetic testing is required to determine if TTR amyloidosis is caused by a hereditary or genetic mutation, or if it’s the result of the wild type of transthyretin. (1)

Once someone is diagnosed, his or her doctor will likely treat the individual with diuretics to limit the kind of fluid buildup that causes limb swelling. A low-salt diet can also help because limiting salt reduces fluid retention.

But treating the heart-related symptoms of wild-type ATTR is more difficult. Standard heart disease medications like beta blockers and calcium channel blockers don’t work well for individuals with wild-type ATTR and so are usually avoided. (3) In patients with potentially deadly heart problems related to wild-type ATTR, a heart transplant may be needed. (1)

There is some research that supplements containing curcumin or genistein (a component of soy) might be helpful. But more study is needed to determine if these supplements are safe and truly effective. (7,8) There are also a number of drugs in development for wild-type ATTR, but so far none have been approved for the treatment of this disease. (3)

In most cases, doctors will use a variety of tests to monitor the progression of an individual’s wild-type ATTR amyloidosis, and they’ll treat any specific symptoms or side effects as they arise (1).

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